Dr Brian McClelland

WS

1. P137 - What effect did each step of these location changes have in terms of potential capacity to produce more Cryo? 

2. P138 - Can he give any idea of capacity increase that he refers to? Double, Triple?

3. P142 - Why would it have been an important consideration?

4. P159 - The first disadvantage he lists for freeze dried cryo about reconstituting and mixing with water, is this not exactly what is done with factor concentrate? So how is that a disadvantage in comparison?

5. P161 - Is he aware of any published factual basis for the hearsay on cryo reactions?

   1. Is he aware that the documentation from the 1960s boasts little no adverse reactions from Cryo? Does he accept it is possible that rather than all these studies from around the world being wrong, he was misinformed?

      1. Sources

         1. "No early or late generalized hypersensitivity reactions occurred, even in three patients who had required corticosteroid or antihistamine cover... and there were no local reactions at the site of injection" …"No other side-effects or reactions were observed"... Link Removed

         2. "cryoprecipitate re­presents an easily prepared factor VIII concentrate with a good haemo­static effect and virtually no side-effects." Link Removed

         3. "Side effects due to cryoprecipitate were uncommon" Link Removed

         4. "So far no patient receiving cryoprecipitate at this hospital has had any adverse reaction, despite the fact that neither Piriton (chlorpheniramine) nor hydrocortisone was given even to those patients who had needed these drugs to cover whole-plasma infusions." Link Removed

         5. "No side effects have been observed in the course of and after transfusions" Link Removed

         6. "no complications were associated with its use" Link Removed

6. P161 - The final sentence, can he clarify whether he is meaning in terms of convenience, and not viral risk? Surely, the more satisfactory product would have been cryo in regard to the latter. He appears to be placing convenience over safety, even in hindsight? why?

7. P162 - Is he aware of any published factual basis for this?

   1. Is he aware that the literature from the 1960s consistently states that cryo had removed the risk of volume overload that could be attended from plasma infusion?

   2. Does he accept any possible risk of volume overload from cryo would be less than plasma?

   3. Is he personally aware of any specific case of Cryo volume overload having occurred? If so, provide details.

      1. Sources:

         1. “"The danger of circulatory overload is minimized because of the small volume given." Link Removed

         2. "The low volume avoids the problem of circulatory overload when enormous quantities of Factor VIII are required" Link Removed

         3. "Cryoprecipitate represents an important acquisition for the treatment of haemophilia A patients, not only because it makes it possible to bring the factor VIII level to any desired value without danger of overloading of the circulation but also because it can be prepared so easily." Link Removed

         4. “"Because of the small volume of the product, the patient's AHG concentration can be increased to any desired level without danger of circulatory overload" Link Removed

8. Might it be the case that the optimism and hope for Factor Concentrate provided an incentive to think of Cryo as being worse than it, in reality was, because concentrates were more convenient in some respects and so to think negatively of Cryo would increase the rationale / justification to use concentrates, even in light of the viral risks?